Background: The natural history of HIV infection and its
progression towards aids may vary considerably among individuals. One of the possible
reasons for this are genetic factors, including single nucleotide polymorphisms
(SNPs). SNPs in promoters of cytokines genes may affect the immune system, but
their impact on the course of HIV infection is currently under investigation.
The present study aimed to evaluate the frequencies and possible effects of
SNPs at positions -589 and -1098 in the IL-4 gene (SNP/pIL-4 -589 and SNP/pIL-4
-1098, respectively) and -238 and -862 in the TNF-α gene (SNP/pTNF-α -238 and
SNP/pTNF-α -862, respectively) in HIV-infected patients from Brazil. Methods: DNA samples from 157 patients were extracted from
peripheral blood mononuclear cells. SNPs genotyping was performed by Real-time
PCR-coupled High Resolution Melting analysis (HRM), along with controls
validated by automated DNA sequencing. Results: Patients carrying TT
at SNP/pIL-4 -589 had lower circulating T CD8+ lymphocytes
(mean= 841.6 cells/mm3, SD= 393.7 cells/mm3) compared to CC carriers (mean= 1,224.0 cells/mm3,
SD= 1,125.0 cells/mm3) (p= 0.0104). On the other hand, carriers of TT at SNP/pIL-4 -1098 had higher
circulating T CD8+ lymphocytes (mean= 1,146.7 cells/mm3,
SD= 852.6 cells/mm3) compared to GT
carriers (mean= 752.5 cells/mm3, SD= 299.6 cells/mm3) (p=
0.0053). Regarding the SNP/pTNF-α -238, GG and GA
proportions were significantly different between patients without antiretroviral
treatment (65% and 35%, respectively) and under treatment and without therapeutic
failure (87.5% and 12.5%, respectively) (p= 0.0205). None of the other
associations evaluated (between the SNPs and age, sex, route for HIV infection,
sexual orientation, estimated time of HIV infection, CDC stage, T CD4+
cells counts, or HIV viremia) was
significant. Conclusions: The results provide
compelling evidence that the presence of SNPs in cytokine-coding genes have an
impact on the natural history of HIV infection, possibly due to changes in the
balance between pro- and anti-inflammatory cytokines.